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Trial registered on ANZCTR


Registration number
ACTRN12614001108606
Ethics application status
Approved
Date submitted
9/10/2014
Date registered
20/10/2014
Date last updated
30/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Quercetin supplementation in adolescents with familial hypercholesterolaemia (FH)
Scientific title
The effect of quercetin supplementation in adolescents with familial hypercholesterolaemia (FH) on flow mediated dilatation of the brachial artery
Secondary ID [1] 285467 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Familial Hypercholesterolaemia 293243 0
Condition category
Condition code
Cardiovascular 293512 293512 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following an overnight fast, participants will undergo baseline measurements of endothelial function, before receiving oral quercetin aglycone (300mg dissolved in water). There will be a 7-day washout period between the intervention and control.
Intervention code [1] 290399 0
Treatment: Other
Comparator / control treatment
Following an overnight fast, participants will undergo baseline measurements of endothelial function, before receiving oral placebo (maltodextrin dissolved in water) at baseline. There will be a 7-day washout period between the intervention and control.
Control group
Placebo

Outcomes
Primary outcome [1] 293328 0
The primary outcome measure is flow-mediated dilatation (FMD), which is measured as the % change in the brachial artery diameter, compared to baseline, following ischaemia. This is measured as the peak response, within five minutes of ischaemia cuff release. Endothelial function measurements will be performed via brachial artery ultrasound by a trained ultrasonographer, blinded to the study treatments. Brachial artery endothelial function will be performed (at the same time of the morning after a 12-hour overnight fast) in a quiet, air-conditioned room with a stable temperature of 220C. Subjects will be requested to refrain from taking their usual medications and from undertaking strenuous exercise on the morning of the visits. The brachial artery will be imaged using high resolution vascular ultrasonography. A pneumatic cuff will be placed around the forearm, distal to the insonated artery. Baseline brachial diameters and blood velocities will be recorded for one minute. The occluding cuff will then be rapidly (1-2 seconds) inflated to a pressure of approximately 50 mmHg above the systolic blood pressure for five minutes. Diameter and blood velocity recordings will be resumed 30 seconds before cuff deflation and continued for 2.5 minutes following cuff release. Ultrasound images will be stored digitally for subsequent analysis using a semiautomated edge-detection software system. Responses will be calculated as percentage change in brachial artery diameter compared with baseline.
Timepoint [1] 293328 0
2 hours post quercetin or placebo
Secondary outcome [1] 310799 0
Acceptability of FMD to adolescents will be assessed using a 5-point Likert scale
Timepoint [1] 310799 0
2 hours post ingestion of quercetin or placebo

Eligibility
Key inclusion criteria
Adolescents with familial hypercholesterolaemia
Minimum age
13 Years
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participant or legal guardian/parent unable to provide an informed consent.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Subjects will be enrolled from the outpatient clinic. The study is a randomised, double-blind, placebo controlled cross-over trial. Allocation concealment will be by sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
a) Participant treatment order will be randomised using computer generated numbers. Each participant will receive their treatment order at their first study visit.
(b) Participants, the study coordinator and the ultrasonographer will all be blinded to the treatments, which will only be identified by code. This code will not be broken until the study is complete and all results have been analysed.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
The study is a randomised, double-blind, placebo controlled cross-over trial.
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Statistical analysis will be performed with the advice of a biostatistician. There will be no interim analysis, and all results will be analysed as comparison of treatment to placebo. As FMD is a repeated measurement taken over a 5min post-ischaemic period, repeated measurement analysis will be performed on each participant. Comparison in FMD response following treatment between groups will be analysed using ANOVA (analysis of variance), following adjustment for baseline. Further adjustment for age, gender and weight may also be considered.
Previous studies within our department, selecting specifically for a reduced FMD response, have indicated that a standard deviation of approximately 2% is expected. It is not unreasonable to expect this will also be the case in the present study, as we are specifically selecting a population of FH patients, at increased risk of CVD, and therefore with an expected reduced FMD response. With a SD of 2%, alpha = 0.05, 10 patients per group will give us more than 80% power to detect a 2% change in FMD response following treatment. We have previously shown that a 2% increase in FMD can be achieved through supplementation with flavonoid rich foods/beverages in adults. A 2% improvement in FMD is also associated with an approximate 25% reduction in CVD risk.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 3040 0
Princess Margaret Hospital - Subiaco

Funding & Sponsors
Funding source category [1] 290071 0
Government body
Name [1] 290071 0
Telethon Perth Children's Hospital Research Fund
Department of Health of Western Australia
Address [1] 290071 0
Department of Health of Western Australia
PO Box 8172
Perth Business Centre
WA 6849
Country [1] 290071 0
Australia
Primary sponsor type
Individual
Name
Dr Andrew Martin
Address
Princess Margaret Hospital for Children
GPO Box D184
Perth
WA 6840
Country
Australia
Secondary sponsor category [1] 288763 0
Hospital
Name [1] 288763 0
Princess Margaret Hospital for Children
Address [1] 288763 0
GPO Box D184
Perth
WA 6840
Country [1] 288763 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291775 0
Princess Margaret Hospital for Children
Ethics committee address [1] 291775 0
GPO Box D184
Perth
WA 6840
Ethics committee country [1] 291775 0
Australia
Date submitted for ethics approval [1] 291775 0
Approval date [1] 291775 0
22/07/2014
Ethics approval number [1] 291775 0
2014037EP

Summary
Brief summary
This project aims to investigate the potential beneficial effect of a natural plant food compound (quercetin), on blood vessel function in adolescents with Familial Hypercholesterolaemia (FH). FH is a common genetic disorder affecting many thousands of children and adolescents throughout Australia, that elevates blood cholesterol from the time of birth, predisposing them to heart disease in early adult life. Untreated, 50% of men and 20% of women will have suffered a fatal or non-fatal cardiovascular event (ie heart attack) by the age of 50.
Children with FH have highly compromised blood vessel function. Whilst medications like statins will lower cholesterol levels and can help improve blood vessel function, there is general reluctance among physicians and parents to commence children with FH on statins before the age of 18 years, because of a lack of long-term follow up studies on the use of these medications in younger patients.
Thus, a nutrition-based supplement that could improve blood vessel function in children and adolescents with FH prior to them going on long term statin therapy would be of benefit. Using non-invasive ultrasound, we will investigate the effect of consuming a drink containing the natural plant food compound quercetin on how the blood vessel functions in 10 adolescents with FH aged 13-18 years. This will be compared to a placebo drink that contains a harmless sugar compound. We expect that the plant food compound will have a beneficial effect on blood vessel function in this population and lead to a potential new treatment option.
Trial website
Trial related presentations / publications
none - manuscript attached
Public notes
Attachments [1] 2925 2925 0 0

Contacts
Principal investigator
Name 51974 0
Dr Andrew Martin
Address 51974 0
Princess Margaret Hospital for Children
GPO Box D184
Perth
WA 6840
Country 51974 0
Australia
Phone 51974 0
+61893408222
Fax 51974 0
Email 51974 0
andrew.martin@health.wa.gov.au
Contact person for public queries
Name 51975 0
Dr Andrew Martin
Address 51975 0
Princess Margaret Hospital for Children
GPO Box D184
Perth
WA 6840
Country 51975 0
Australia
Phone 51975 0
+61893408222
Fax 51975 0
Email 51975 0
andrew.martin@health.wa.gov.au
Contact person for scientific queries
Name 51976 0
Dr Andrew Martin
Address 51976 0
Princess Margaret Hospital for Children
GPO Box D184
Perth
WA 6840
Country 51976 0
Australia
Phone 51976 0
+61893408222
Fax 51976 0
Email 51976 0
andrew.martin@health.wa.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary